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C Lance-Jones

Publications and source records attributed to C Lance-Jones.

At least 19 recordsLinked to original sources
PubMed2004

Loss of the Sall3 gene leads to palate deficiency, abnormalities in cranial nerves, and perinatal lethality.

Members of the Spalt gene family encode putative transcription factors characterized by seven to nine C2H2 zinc finger motifs. Four genes have been identified in mice--Spalt1 to Spalt4 (Sall1 to Sall4). Spalt homologues are widely expressed in neural and mesodermal tissues during early embryogenesis. Sall3 is normally expressed in mice from embryonic day 7 (E7) in the neural ectoderm and primitive streak and subsequently in the brain, peripheral nerves, spinal cord, limb buds, palate, heart, and otic vesicles. We have generated a targeted disruption of Sall3 in mice. Homozygous mutant animals die on the first postnatal day and fail to feed. Examination of the oral structures of these animals revealed that abnormalities were present in the palate and epiglottis from E16.5. In E10.5 embryos, deficiencies in cranial nerves that normally innervate oral structures, particularly the glossopharyngeal nerve (IX), were observed. These studies indicate that Sall3 is required for the development of nerves that are derived from the hindbrain and for the formation of adjacent branchial arch derivatives.

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PubMed2001

Hoxd10 induction and regionalization in the developing lumbosacral spinal cord.

We have used Hoxd10 expression as a primary marker of the lumbosacral region to examine the early programming of regional characteristics within the posterior spinal cord of the chick embryo. Hoxd10 is uniquely expressed at a high level in the lumbosacral cord, from the earliest stages of motor column formation through stages of motoneuron axon outgrowth. To define the time period when this gene pattern is determined, we assessed Hoxd10 expression after transposition of lumbosacral and thoracic segments at early neural tube stages. We present evidence that there is an early prepattern for Hoxd10 expression in the lumbosacral neural tube; a prepattern that is established at or before stages of neural tube closure. Cells within more posterior lumbosacral segments have a greater ability to develop high level Hoxd10 expression than the most anterior lumbosacral segments or thoracic segments. During subsequent neural tube stages, this prepattern is amplified and stabilized by environmental signals such that all lumbosacral segments acquire the ability to develop high levels of Hoxd10, independent of their axial environment. Results from experiments in which posterior neural segments and/or paraxial mesoderm segments were placed at different axial levels suggest that signals setting Hoxd10 expression form a decreasing posterior-to-anterior gradient. Our experiments do not, however, implicate adjacent paraxial mesoderm as the only source of graded signals. We suggest, instead, that signals from more posterior embryonic regions influence Hoxd10 expression after the early establishment of a regional prepattern. Concurrent analyses of patterns of LIM proteins and motor column organization after experimental surgeries suggest that the programming of these characteristics follows similar rules.

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PubMed1998

Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression.

Motor function depends on the formation of selective connections between sensory and motor neurons and their muscle targets. The molecular basis of the specificity inherent in this sensory-motor circuit remains unclear. We show that motor neuron pools and subsets of muscle sensory afferents can be defined by the expression of ETS genes, notably PEA3 and ER81. There is a matching in PEA3 and ER81 expression by functionally interconnected sensory and motor neurons. ETS gene expression by motor and sensory neurons fails to occur after limb ablation, suggesting that their expression is coordinated by signals from the periphery. ETS genes may therefore participate in the development of selective sensory-motor circuits in the spinal cord.

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PubMed1996

A critical period for the specification of motor pools in the chick lumbosacral spinal cord.

When 3-4 segments of the chick lumbosacral neural tube are reversed in the anterior-posterior axis at stage 15 (embryonic day 2.5), the spinal cord develops with a reversed organization of motoneurons projecting to individual muscles in the limb (C. Lance-Jones and L. Landmesser (1980) J. Physiol. 302, 581-602). This finding indicated that motoneuron precursors or components of their local environment were specified with respect to target by stage 15. To identify the timing of this event, we have now assessed motoneuron projections after equivalent neural tube reversals at earlier stages of development. Lumbosacral neural tube segments 1-3 (+/- one segment cranial or caudal) were reversed in the anterior-posterior axis at stages 13 and 14 (embryonic day 2). The locations of motoneurons innervating two thigh muscles, the sartorius and femorotibialis, were mapped via retrograde horseradish peroxidase labeling at stages 35-36 (embryonic days 9-10). In a sample of embryos, counts were made of the total number of motoneurons in the lateral motor columns of reversed segments. The majority of motoneurons projecting to the sartorius and femorotibialis were in a normal position within the spinal cord. Segmental differences in motor column size were also similar to normal. These observations indicate that positional cues external to the LS neural tube can affect motoneuron commitment and number at stages 13-14. Since these observations stand in contrast to results following stage 15 reversals, we conclude that regional differences related to motoneuron target identity are normally specified or stabilized within the anterior LS neural tube between stages 14 and 15. To examine the role of the notochord in this process, neural tube reversals were performed at stages 13-14 as described above, except that the underlying notochord was also reversed. Projections to the sartorius and femorotibialis muscles did not differ significantly from those in embryos with neural tube reversals alone, indicating that the notochord is not the source of cues for target identity at stages 13-14.

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PubMed1995

Müller glia stabilizes cell columns during retinal development: lateral cell migration but not neuropil growth is inhibited in mixed chick-quail retinospheroids.

Radial columnar organization of cell clones is a characteristic feature of vertebrate retinae that is structurally not understood. Here we provide in vitro evidence that Müller glia processes stabilize cells within columns. Dissociated embryonic chick retinal plus pigmented cells regenerate in vitro into fully laminated stratospheroids. After reaggregating chick and quail cells, quail-derived spheroid areas are detected as isolated sectors, as shown by a quail-specific antibody. Each sector contains one or multiple cell columns. The radial borders separating chick and quail sectors are fully congruent with the extension of 3A7-labelled Müller glia processes. While cell somata do not show any lateral interspecies mixing, quail-derived neuropil extends within the inner plexiform areas far into chick sectors. After selective damage of Müller cells by the gliotoxin DL-alpha-aminoadipic acid, the columnar organization is destabilized, as evidenced by a decrease in vimentin expression and by the migration of individual neurons out of their cell column. These data demonstrate that Müller cells actively stabilize cells within their columns, while neuritic growth is not hindered.

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PubMed1995

Specifying the target identity of motoneurons.

In the vertebrate spinal cord, motoneurons are clustered into longitudinal columns in agreement with the targets they innervate. Motoneurons within each column acquire properties early in development that ensure their axons navigate to appropriate targets, but how this target identity is specified is unknown. Recently, Tsuchida et al. described the expression of putative regulatory genes within motor columns in the chicken spinal cord. Combinations of LIM-family homeobox genes differentially mark columns that project to distinct target groups. Expression precedes column formation and axon outgrowth, making these genes candidates for specifying the target identity of motoneuron groups.

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PubMed1995

Slow and fast muscle fibers are preferentially derived from myoblasts migrating into the chick limb bud at different developmental times.

Avian limb myoblasts originate from somites and migrate into the periphery during limb bud formation. It is not known how these precursors become arranged into a stereotyped pattern of muscles and primary fiber types. We used in vivo surgical transplantation and anatomical analyses of thigh muscle patterns to ask whether myoblasts migrating into the limb bud at different developmental times adopt different fates. When myoblast migration was interrupted by transplanting limb bud tissue to the coelomic cavity of a host embryo early in the migratory period (stages 16-early 17), few thigh muscles were found at stages 30-33. Primordia that were present corresponded to muscles that normally contain a majority of slow myotubes. In limbs transplanted slightly later (stages late 17-18), the only missing muscles were those that normally contain the highest numbers of fast myotubes. Parallel results were obtained in chimeric limbs made by transplanting a quail limb bud to a chick host at different times during the migratory period, an experimental situation in which the limbs were not depleted of muscle precursors or nerves. These findings suggest that the earliest myoblast migrants give rise mainly to slow primary myotubes, the later migrants to fast myotubes. To determine whether the early limb bud environment defines the fate of migrating myoblasts, we assessed fiber type patterns in limbs that developed from young limb bud tissue (stages 15-early 16) transplanted to older hosts (stage 17). A significant depletion of slow myosin-positive profiles was found within slow muscles. Fast muscles were generally normal in size. These results provide in vivo evidence that limb myoblast diversity arises prior to the entry of myoblasts into the limb. We suggest that there is a gradual change in the proportions of myoblasts capable of forming slow and fast fiber types, a change which may begin in the somites or early in the migratory period.

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PubMed1991

The influence of presumptive limb connective tissue on motoneuron axon guidance.

During embryogenesis in the chick, the lumbosacral (LS) somatopleure gives rise to the connective tissue and the epidermis of the limb. We wished to determine if the LS somatopleure was a primary source of guidance cues for motoneuron pathway choices along the anteroposterior axis of the limb. At stage (st) 15, prior to its population by muscle cell precursors and the neural crest, the LS somatopleure was shifted anteriorly. This surgery resulted in the development of limbs that were shifted one to four segments into the thoracic region. Muscles within the anterior thigh of the shifted limb were normally patterned and of composite origin: connective tissues were of LS origin, while muscle cells were of LS and thoracic origin. Retrograde HRP labeling at st 35-37 indicated that motoneuron pools to these anterior thigh muscles were located within LS rather than thoracic cord segments. Pools to individual muscles were smaller than normal but occupied segmental and transverse positions in the LS cord that generally matched those of normal embryos. These findings suggest that individual muscles within somatopleure-shifted limbs are innervated specifically and are in accord with their connective tissue (and epidermal) level of origin. Reconstructions of nerve patterns at st 28-31 suggested that LS motoneurons corrected for the shift by altering their pathways at midthigh regions. We conclude that the somatopleure, and most likely its connective tissue component, contains the information for setting up a specific axon guidance system in the developing limb.

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PubMed1988

Development of neuromuscular connections: guidance of motoneuron axons to muscles in the embryonic chick hindlimb.

A striking feature of the outgrowth of motor axons from the embryonic chick spinal cord is the accuracy with which they grow to correct target muscles in the limb. Studies involving the surgical manipulation of the early neural tube or limb bud have led to the conclusion that motoneurons are specified or acquire distinctive properties early in development that enable them to detect and respond to specific cues in the periphery. We have recently carried out studies to identify the cells or tissues responsible for producing these cues. Major contributors to the outgrowing axon's environment are the lumbosacral (LS) somites which give rise to limb muscle cells and the LS somatopleural mesoderm which gives rise to limb connective tissues. To determine whether the LS somites contain specific guidance information at stages when motoneurons are known to be specified, motor projections were assessed in chick embryos after early somitic tissue reversals. The finding of normal projection patterns suggests that the LS somites do not contain such information at early stages. To assess the role of the LS somatopleural mesoderm in specific axon guidance, we examined motor projections in embryos where the LS somatopleural mesoderm had been shifted anteriorly before limb bud formation. In these embryos the limb developed in an anteriorly shifted position. LS motoneuron axons entered the posterior part of the limb but then extended anteriorly along aberrant paths to innervate appropriate muscles. These observations suggest that it is the precursor of limb connective tissues that is the source of specific axon guidance cues.

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PubMed1988

The somitic level of origin of embryonic chick hindlimb muscles.

Studies of avian chimeras made by transplanting groups of quail somites into chick embryos have consistently shown that the muscle cells of the hindlimb are derived from the adjacent somites, however, the pattern of cell distribution from individual somites to individual hindlimb muscles has not been characterized. I have mapped quail cell distribution in the chick hindlimb after single somite transplantation to determine if cells from an individual somite populate discrete limb muscle regions and if there is a spatial correspondence between a muscle's somitic level of origin and the known spinal cord position of its motoneuron pool. At stages 15-18 single chick somites or equivalent lengths of unsegmented somitic mesoderm adjacent to the prospective hindlimb region were replaced with the corresponding tissue from quail embryos. At stages 28-34, quail cell distribution was mapped within individual thigh muscles and shank muscle regions. A quail-specific antiserum and Feulgen staining were used to identify quail cells. Transplants from somite levels 26-33 each gave rise to consistent quail cell labeling in a unique subset of limb muscles. The anteroposterior positions of these subsets corresponded to that of the transplanted somitic tissue. For example, more anterior or anteromedial thigh muscles contained quail cells when more anterior somitic tissue had been transplanted. For the majority of thigh muscles studied and for shank muscle groups, there was also a clear correlation between somitic level of origin and motoneuron pool position. These data are compatible with the hypothesis that motoneurons and the muscle cells of their targets share axial position labels. The question of whether motoneurons from a specific spinal cord segment recognize and consequently innervate muscle cells derived from the same axial level during early axon outgrowth is addressed in the accompanying paper (C. Lance-Jones, 1988, Dev. Biol. 126, 408-419). Quail cell distribution was also mapped in chick embryos in which quail somites or unsegmented mesoderm had been placed 2-3 somites away from their position of origin. In all cases donor somitic tissues contributed to muscles in accord with their host position. These results indicate that muscle cell precursors within the somites are not specified to migrate to a predetermined target region.

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PubMed1988

The effect of somite manipulation on the development of motoneuron projection patterns in the embryonic chick hindlimb.

Although the formation of motoneuron projections to individual muscles in the embryonic chick hindlimb has been shown to involve the specific recognition of environmental cues, the source of these cues and their mode of acquisition are not known. I show in the accompanying paper (C. Lance-Jones, 1988, Dev. Biol. 126, 394-407) that there is a correlation between the segmental level of origin of motoneurons and the somitic level of origin of the muscle cells of their targets in the chick hindlimb. These data are compatible with the hypothesis that the developmental basis for specific recognition is a positional one. Motoneurons and myogenic cells may be uniquely labeled in accord with their axial level of origin early in development and subsequently matched on the basis of these labels. To test this hypothesis, I have assessed motoneuron projection patterns in the embryonic chick hindlimb after somitic tissue manipulations. In one series of embryos, somitic mesoderm at levels 26-29 or 27-29 was reversed about the anteroposterior axis prior to myogenic cell migration and axon outgrowth. Since previous studies have shown that cells migrate from the somites in accord with their position and that somites 26-29 populate anterior thigh musculature, this operation will have reversed the somitic level of origin of anterior thigh muscles. Retrograde HRP labeling of projections to anterior thigh muscles at stage (st) 30 and st 35-38 showed that motoneuron projections were largely normal. This finding suggests that limb muscle cells or their source, the somites, do not contain the cues responsible for specific recognition prior to myogenic cell migration and axon outgrowth. To confirm that specific guidance cues were still intact after somitic mesoderm reversal, I also assessed motoneuron projections in embryos where somitic tissue plus adjacent spinal cord segments at levels 26-29 were reversed in a similar manner. Analyses of the distribution of retrogradely labeled motoneurons in reversed cord segments at st 35-36 indicated that motoneuron projections were reversed. This finding suggests that motoneurons have altered their course to project to correct targets despite the altered somitic origin of their targets and, thus, that specific guidance cues were intact. I conclude that if cues governing target or pathway choice are encoded positionally then they must be associated with other embryonic tissues such as the connective tissues or that guidance cues are acquired by myogenic cells after the onset of migration and motoneuron specification.

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PubMed1988

Motoneuron axon guidance: development of specific projections to two muscles in the embryonic chick limb.

In the embryonic chick limb, multiple mechanisms are believed to be responsible for a precise guidance of motoneuron axons to their appropriate targets from the earliest stages of axon outgrowth. In this report, I discuss one of these guidance mechanisms; a mechanism which appears to depend on a prelabeling of motoneurons prior to axon outgrowth. By focusing on the development of axonal projections to two specific muscles, I review the evidence that motoneurons destined for each muscle actively recognize environmental cues, and discuss recent experiments designed to identify the source of these cues.

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PubMed1986

The development of sensory projection patterns in embryonic chick hindlimb under experimental conditions.

In the chick, sensory neurons grow to their segmentally appropriate target sites in the hindlimb from the outset during normal development. To elucidate the underlying mechanisms, we performed various manipulations of the neural tube, including the neural crest, or of the hindlimb, before axonal outgrowth and assessed the resulting sensory projections using retrograde and anterograde HRP labeling and electrophysiological techniques. Previous experiments had shown that motoneurons are specified to project to their appropriate target muscles prior to axon outgrowth and that they respond to cues in the limb in order to grow to those targets (C. Lance-Jones and L. Landmesser, 1980, J. Physiol. (London) 302, 559-602; C. Lance-Jones and L. Landmesser, 1981, Proc. R. Soc. London, B 214, 19-52). When several segments of neural tube and neural crest were deleted, sensory neurons in the remaining segments still projected along their correct pathways, as did motoneurons. In situations in which motoneurons grew to their correct targets from altered positions with respect to the limb (e.g., small neural tube reversals), sensory neurons also tended to project along the segmentally appropriate pathways both to skin and to muscle. In situations in which motoneurons were displaced greater distances from their normal point of entry into the limb and made wrong connections (e.g., large neural tube reversals, anterior-posterior limb reversals), sensory neurons also projected incorrectly. The patterns of sensory projections to muscles were, in each situation, generally similar to the motoneuron projections. These results are consistent with the possibility that sensory neurons, like motoneurons, are specified with respect to their peripheral connectivity. Alternatively, the results suggest that motoneurons may play a role in the process of pathway selection by sensory neurons.

Afferent Pathways↗
PubMed1982

Motoneuron cell death in the developing lumbar spinal cord of the mouse.

Motoneuron cell death in the lumbar lateral motor column of the mouse embryo and neonate was examined to determine the timing and position of cell death with respect to events occurring in the limb. Counts of motoneurons in histological sections of the entire lumbar lateral motor column were made in mice ranging in age from 12 1/2 days of embryonic development to 20 days of neonatal life. Between 13 and 18 days of embryonic development, 67% of the motoneurons initially present in the motor column die, or approximately 3350 out of 5000 cells. Peak motoneuron cell death occurs at 14 days. No cell death occurs during the first neonatal weeks when polyneuronal muscle fiber innervation is lost. Counts of the total number of cells present at 18 days were similar to those previously reported for adult mice, suggesting that all motoneuron cell death has occurred by the end of prenatal development. In a few 13- to 14-day mouse embryos, the hindlimbs were totally filled with horseradish peroxidase (HRP) to define the boundaries and size of the lateral motor population which projects to the limb at early stages. Counts of HRP labeled motoneurons in selected lumbar cord segments were close to the total number of lateral motoneurons in the same segments. As the HRP injections were made prior to or at the onset of cell death, these observations indicate that many cells which die have sent axons into the limb.

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PubMed1981

Pathway selection by chick lumbosacral motoneurons during normal development.

Pathways taken by motoneuron axons from the lumbosacral lateral motor column to individual hindlimb muscles have been characterized throughout the normal period of outgrowth and the establishment of specific functional connections in the chick embryo. Axon pathways from individual cord segments were identified after injections of horseradish peroxidase (HRP) directly into the cord. Labelled motoneuron axons were then traced through the plexus and major nerve trunks to termination sites within the limb. At stages 23-24 labelled axons within spinal nerves have just reached the base of the limb and have begun to converge and form the crural and the ischiadic plexus. Even at this early stage, before periods of muscle cleavage, motoneuron cell death and muscle nerve formation, axons show no evidence of widespread random distribution within the limb. Rather, they generally maintain their anterior-posterior position as far as the base of the limb. At stages 27-30, although axons to individual muscles were found to course in discrete tracts within the plexus and nerve trunks they also changed their topographical position with respect to other axons. Axon pathways to single muscles were characterized by tracing retrogradely labelled axons back to the cord after injections of HRP into specific muscle nerves. Axons destined for a single muscle are intermingled with other axons in the spinal nerves and proximal plexus but by the distal plexus have converged to form a discrete tract which then diverges as an individual muscle nerve at more distal levels. These observations exclude models for the establishment of specific connections in which there is widespread testing of the environment with removal of projection errors by cell death and/or axon retraction. They also exclude models that require axons to maintain their topographical position with respect to each other throughout their course.

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PubMed1981

Pathway selection by embryonic chick motoneurons in an experimentally altered environment.

To characterize cues used by motoneuron axons to reach their appropriate targets, connectivity patterns within the embryonic chick hindlimb have been analysed after early experimental manipulations of the limb or spinal cord. The manipulations altered the anterior-posterior (a.-p.) relationship between motoneurons within the lumbosacral motor column and their specific targets in the limb. Primary emphasis was placed on analysing the pathways taken by embryonic motoneuron axons at stages 23-36 which had been orthogradely labelled by horseradish peroxidase (HRP) injection into the motor column. Motoneuron pool topography and functional patterns of connectivity were also identified by retrograde HRP labelling and spinal cord stimulation coupled with electromyographic recording. With small shifts in position, as in two or three segment a.-p. cord reversals or a.-p. limb shifts, motoneuron axons frequently entered the appropriate plexus but in an inappropriate spinal nerve sequence. Despite this, axons altered their course to innervate specifically and consistently their current target. When motoneuron axons entered an inappropriate plexus as the result of a greater positional shift (i.e. more extensive cord reversal or limb shift) or in experiments where posterior cord segments were replaced with anterior cord segments and supernumerary limbs were added, they behaved in one of two ways. They either formed inappropriate and largely unpatterned or unordered connections or they took totally aberrant paths within the limb to reach their appropriate target. We conclude that axons are capable of responding in a precise and specific manner to environmental cues when displaced up to a certain distance from their target or normal point of entry into the limb. Their failure to form patterned connections at more extreme distances suggests that the cues to which they are responding may be local, or that an axon's ability to respond to them is restricted to subclasses of the motoneuron population.

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PubMed1980

Motoneurone projection patterns in embryonic chick limbs following partial deletions of the spinal cord.

1. Several anterior segments of the lumbosacral spinal cord were deleted in a series of St. 15-16 chick embryos, which is prior to the birthdate of the motoneurones and to limb bud formation. Deleted segments did not regenerate and therefore some muscles were deprived of their normal source of innervation. 2. The projection pattern of motoneurones in remaining lumbosacral segments was assessed electrophsiologically (St. 30-36) and by orthograde and retrograde labelling of motoneurones with horseradish peroxidase (St. 24-36) from the time that axons first enter the limb until after the normal motoneurone cell death period. 3. The projection pattern of remaining segments was not altered by the deletion. At no time did inappropriate segments innervate muscles or regions of the primary muscle mass which had had their enter innervation source removed by the deletion, although they often innervated immediately adjacent regions. 4. The pathways taken by remaining motoneurones both in the plexus and muscle nerves were not different from their normal control pattern. From the time that axons first reached the base of the limb, there was no evidence that they compensated for missing spinal nerves by projecting down inappropriate pathways. 5. With respect to pathway selection, we can conclude that axons are normally not excluded from certain pathways by interactions with other axons, nor do they interact amongst each other in distributing themselves to all available pathways. 6. We can also conclude that once axons enter a muscle or muscle mass, they are not kept within appropriate regions by competition with axons that normally occupy adjacent regions. In summary we can exclude both the process of competition and a timed outgrowth mechanism as playing a major role in the development of specific motor connexions in the chick hind limb. 7. Muscles totally deprived of their innervation by the deletion underwent cleavage, became contractile and appeared to differentiate normally until St. 20. However by St. 35 they had become extremely atrophic. 8. In some cases following the deletion of part of a motoneurone pool, the number of motoneurones per unit of cord in the remaining pool at St. 35-36 was significantly greater than control values. Since these motoneurones were located in the position (both rostro-caudal and transverse) of the control motoneurone pool, we conclude that we were able to rescue some of the neurones that would normally have died during the motoneurone cell death period (St. 30-35).

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